In response to PA-12-281, HIV/AIDS, Drug Use, and Vulnerable Populations in the US (R01), we propose an effectiveness trial among persons triply diagnosed (mental illness, substance abuse, HIV) recruited from two inpatient psychiatric units within the University of Pennsylvania Health System (UPHS). Despite general recognition that persons with serious mental illness (SMI) are at heightened risk to contract and transmit human immunodeficiency virus (HIV), systematic HIV testing in mental health settings is rare. Using discarded bloods samples over a six month period, our research team (Rothbard et al., 2008) found in excess of 10% HIV seroprevalence in two inpatient psychiatric units in Philadelphia, the Wright 4 Unit at Presbyterian Hospital and the 4 Spruce Unit of Pennsylvania Hospital where the proposed study will occur. We argued then that HIV testing should be routinely conducted in those settings. In a five year longitudinal effectiveness trial, we will identify HIV positive SMI inpatients through rapid testing. Those who are newly diagnosed or who were previously diagnosed but not currently engaged in HIV treatment and who also are substance using will be offered an opportunity to participate in a randomized community trial. Previously we have conducted a Phase II trial of PATH for Positives (PFP) in which we observed broad and far-reaching effects of an intervention utilizing a nurse health navigator (NHN) model for HIV+ SMI clients. This proposal builds on what we learned previously to provide a nurse health navigator (NHN) model as integrated treatment of the targeted individuals in real world conditions and to monitor the implementation of PATH for Triples (PFT). The target population is arguably among the highest risk patient populations for poor treatment outcomes. Based on past experience, we expect to enroll about 75% of those eligible on a rolling basis, or ~240 participants who will then be randomized. This will yield ~120 PFT and ~120 TAU participants over a 36 month recruitment before attrition. A similar population in PFP resulted in a 17% attrition rate, so we estimate complete data for at least 75% of participants resulting in a complete dataset of ~180 participants (90 PFT, and 90 TAU). PFT participants will receive NHN services for 12 months. Data will be collected at baseline, 6, 12, and 18 months for each participant. Participants will be followed longitudinally for an additional 6 months post intervention to measure any decay of the intervention after it is withdrawn. Experimental participants will begin PFT while still receiving inpatient services and the project nurses will participate in discharge planning and facilitate linkage to Mental Health (MH), Substance Abuse (SA), and Infectious Disease (ID) care in the Philadelphia community. The NHN will also meet at least weekly with the experimental participants to implement the adherence component of PFT using approaches tailored to the communication and comprehension of the person that includes memory aids, education regarding side effects and other treatment aspects, engagement with participants' social networks and treatment providers, and active community outreach. PFT will be implemented for 12 months and participants will be followed for an additional 6 months to allow examination of potential decay of the intervention after it is withdrawn. We expect better retention in treatment for PFT participants and other outcomes include viral load, CD4, indicators of psychological and social functioning, and cost effectiveness.